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Research Program. Precision Nutrition and Cancer

Director: Dr. Ana Ramírez de Molina

Objectives:  according to the most recent data published by leading authorities, a high percentage of cancer cases may be preventable. Diet and life style are key factors in cancer prevention, but also exert essential function as coadjutants for cancer patients during and after therapy. Metabolic reprogramming is a hallmark of cancer in which nutritional strategies might play a key role. Thus, it is necessary to develop personalized treatments based in molecular and metabolic alterations, combining complementary precision medicine and nutrition. We understand Precision Nutrition for cancer as highly efficiency products and strategies personalized for specific physiological conditions and population groups. This new way of understand Nutritional Sciences addresses different areas of knowledge including the precise (molecular) mechanism of action of bioactive compounds present in foods, the genetic profile and its impact in the personal susceptibility to develop cancer and respond to specific treatments, as well as the development of specific strategies for current personal physiological conditions.

Molecular Oncology Group

Group leader: Dr. Ana Ramírez de Molina

Objectives: the group is currently focused on three research topics:

  • Lipid metabolism disorders in cancer: identification of new biomarkers and therapeutic
    targets in diet-related tumors. In this subject, the work of our group mainly focuses on the analysis of lipid metabolism alterations in cancer. Most specifically, we aim at studying the special energetic and structural requirements of tumor cells as well as identifying novel biomarkers of progression and response to therapy, which may represent new therapeutic targets. To this end, in close collaboration with the divisions of Medical Oncology from several
    hospitals, we analyze clinical samples from cancer patients using state-of-the-art genomic
    approaches.

    Gene expression analysis, identification of gene variants and epigenetic regulation by microRNAs of lipid metabolism pathways are then used to study their association with the clinical outcome of the disease. Furthermore, we perform functional studies both using conventional and three-dimensional cell culture such as organoids, and animal models to investigate the role of identified genes and microRNAs. We are especially interested in identifying metabolic profiles associated to the disease progression and analyzing their role from in-vitro cell systems to cancer patients. These analyses are mainly focused on the identification of metabolic pathways and distinctive oncometabolites that may constitute novel markers and targets for the development of future cancer therapies, as well as the genetic basis of the relationship between obesity, associated metabolic disorders and cancer.

  • Activity and mechanism of action of bioactive compounds as potential effective dietary
    supplements in cancer prevention and treatment. We evaluate the activity and molecular mechanism of action of bioactive compounds that may have a therapeutic use in cancer, either alone or in combination with existing chemotherapy. The aim is to establish the scientific basis for the development of nutritional supplements that may exert a beneficial effect on the disease. In close collaboration with the Bioactive Food Ingredients Group from the Research Institute of Food Science (CIAL, CSIC-UAM), we design and characterize different formulations of bioactive compounds. We combine genomics and functional studies in cell lines and intestinal organoids to determine the effect and target populations for personalized therapeutic use of these formulations.

    These products are further evaluated in animal models and finally, in clinical trials in healthy volunteers or cancer patients. Recently, we have evaluated the antitumor effect of a supercritical extract of rosemary approved as safe for human use by EFSA. Such extract inhibits proliferation, induces cell death, and potentiates the effect of chemotherapy, both in sensitive and resistant colon cancer cells. Its formulation for human consumption shows an immunomodulatory effect in healthy volunteers and it is currently being used in a phase-I clinical trial in cancer patients.


Members

Visiting researchers

Dr. Elena María Arranz Gutiérrez
University of Guelph(Canada)
Food Science Department


Students

Jesús del Barrio Morán
Marta Blanco López
Amanda Sousa
Diego Portillo Liso
Irene Marina Beltrán de Heredia Anguita


Clinical Oncology Group

Group leader: Dr. Enrique Casado Sánz and Dr. Jaime Feliú Batle

Objectives: Cancer is a complex disease, whose characteristics, prognosis and response to different treatments depends on several factors, including the patient’s genome, environmental causes such as exposure to contaminants, and microenvironmental causes such as nutritional status or immunological condition of the patient; This complexity makes it imperative that cancer research must be done in a  multidisciplinary way and with the joint efforts of many researchers.

Under the premise that diet and lifestyle are key factors in both cancer prevention and treatment, and in close collaboration with the other groups that are part of the Precision Nutrition and Cancer Program, the Clinical Oncology Group focuses its work on research in patient groups that voluntarily accept to participate in the study of new methods of treating cancer. In general, it is accepted that in the last decades the continuous improvement of the results in the treatment of cancer is due to the realization of clinical trials with new drugs. Similarly, our line of research focused in cancer-oriented nutrigenomics aims to deepen in the knowledge of this pathology by studying highly efficiency products and personalized strategies focused on the implementation of a Precision Nutrition that complements individualized cancer treatments. To do this, we design and carry out clinical trials and nutritional studies that seek to find better ways to prevent, diagnose and treat cancer.

Members

Molecular Immunonutrition Group

Group leader: Dr. Moisés Laparra Llopis

Objectives: immunonutritional-based precision intervention strategies to a selective and driven modulation
of innate immune responses preventing/treating the risk for severity of liver-related diseases and
antitumoral response (s).
Cereals, legumes and other grains have been shown to contain several different protease inhibitors, which
have been assigned to different families on the basis of amino acid sequence similarities. These molecules
play important roles as defensive agents against insects and pests, but also potentially deleterious/
beneficial effects in human nutrition and immune function.

The latter represent greatest stimulus for Dr. Laparra’s research. Particularly, his research approaches the naturally powerful immunostimulatory property of toll-like receptors (TLRs) agonists for active immunotherapy against liver metabolic dysfunction and cancer promotion. Here, a better understanding and use of the immunonutritional-mediated TLR activation can greatly impact the functional differentiation and polarization of macrophages, as relevant prognostic biomarkers of tissue damage and tumor progression.

Additionally, the selective and driven metabolic programming of antigen presenting cells have important roles in the regulation of CD4+T cells priming as well as immune checkpoint blockade. Thereby, preventing effector CD8+T cells exhaustion and longer anti-tumoral response(s). A clear example is the activation of intestinal innate immune responses via TLR4 by defined non-gluten members of the α-amylase/trypsin inhibitors family, present in wheat endosperm and the source of flour. Besides, Dr. Laparra’s research provided significant contributions demonstrating that defined prebiotic structures modulate TLR4 innate immune responses, but normalizes the plasmatic concentrations of phospholipids, central in the setting of therapeutic effects.

Additionally, his research line contributed with effective immunonutritional interventions to promote an anti-inflammatory environment advantageous to CD8+ effector T cells development and reduce hepatic macrophages infiltration. These effects on macrophages, central in coordinating innate immune  responses, were associated to changes in the expression of the fatty acid receptor, recently associated to regulation of metastasic penetrance and tumor growth. The extent to which immunonutritional-based modulation can be translated into physiological benefits for large groups of population affected by liver-related diseases is a central objective of this research line.

Members